3-38496513-C-T

Variant names:

• chr3-38496513-C-T
• rs373135233
• NM_005107.4:c.146C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_005107.4(EXOG):​c.146C>T​(p.Thr49Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T49R) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: EXOG NM_005107.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0820
• Publications: 0 publications found

Genes affected

EXOG (HGNC:3347): (exo/endonuclease G) This gene encodes an endo/exonuclease with 5'-3' exonuclease activity. The encoded enzyme catalyzes the hydrolysis of ester linkages at the 5' end of a nucleic acid chain. This enzyme is localized to the mitochondria and may play a role in programmed cell death. Alternatively spliced transcript variants have been described. A pseudogene exists on chromosome 18. [provided by RefSeq, Feb 2009]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.059970856).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005107.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EXOG	NM_005107.4	MANE Select	c.146C>T	p.Thr49Ile	missense	Exon 1 of 6	NP_005098.2	Q9Y2C4-1
	EXOG	NM_001145464.2		c.146C>T	p.Thr49Ile	missense	Exon 1 of 5	NP_001138936.1	Q9Y2C4-4
	EXOG	NR_134938.2		n.174C>T		non_coding_transcript_exon	Exon 1 of 8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	EXOG	ENST00000287675.10	TSL:1 MANE Select	c.146C>T	p.Thr49Ile	missense	Exon 1 of 6	ENSP00000287675.5	Q9Y2C4-1
	EXOG	ENST00000412107.5	TSL:1	n.146C>T		non_coding_transcript_exon	Exon 1 of 8	ENSP00000400239.1	F2Z2D3
	EXOG	ENST00000431472.5	TSL:1	n.146C>T		non_coding_transcript_exon	Exon 1 of 7	ENSP00000394977.1	F8WE28

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.090
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Benign	0.17	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.079	N
LIST_S2	Benign	0.69	T
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.060	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.69	N
PhyloP100		0.082
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-0.64	N
REVEL	Benign	0.038
Sift	Benign	0.22	T
Sift4G	Benign	0.20	T
Polyphen		0.012	B
Vest4		0.15
MutPred		0.36		Loss of phosphorylation at T49 (P = 0.0388)
MVP		0.19
MPC		0.17
ClinPred		0.069	T
GERP RS		1.8
PromoterAI		0.037	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.028
gMVP		0.48
Mutation Taster		=290/10	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs373135233; hg19: chr3-38538004;